Burtkelleher6357

Kleine-Levin syndrome (KLS) is a rare disorder characterized by severe episodic hypersomnia, with cognitive impairment accompanied by apathy or disinhibition. Pathophysiology is unknown, although imaging studies indicate decreased activity in hypothalamic/thalamic areas during episodes. Familial occurrence is increased, and risk is associated with reports of a difficult birth. We conducted a worldwide case-control genome-wide association study in 673 KLS cases collected over 14 y, and ethnically matched 15,341 control individuals. We found a strong genome-wide significant association (rs71947865, Odds Ratio [OR] = 1.48, P = 8.6 × 10-9) within the 3'region of TRANK1 gene locus, previously associated with bipolar disorder and schizophrenia. Strikingly, KLS cases with rs71947865 variant had significantly increased reports of a difficult birth. TMP269 manufacturer As perinatal outcomes have dramatically improved over the last 40 y, we further stratified our sample by birth years and found that recent cases had a significantly reduced rs71947865 association. While the rs71947865 association did not replicate in the entire follow-up sample of 171 KLS cases, rs71947865 was significantly associated with KLS in the subset follow-up sample of 59 KLS cases who reported birth difficulties (OR = 1.54, P = 0.01). Genetic liability of KLS as explained by polygenic risk scores was increased (pseudo R 2 = 0.15; P less then 2.0 × 10-22 at P = 0.5 threshold) in the follow-up sample. Pathway analysis of genetic associations identified enrichment of circadian regulation pathway genes in KLS cases. Our results suggest links between KLS, circadian regulation, and bipolar disorder, and indicate that the TRANK1 polymorphisms in conjunction with reported birth difficulties may predispose to KLS.Foraging at elevated rates to provision offspring is thought to be an energetically costly activity and it has been suggested that there are physiological costs associated with the high workload involved. However, for the most part, evidence for costs of increased foraging and/or reproductive effort is weak. Furthermore, despite some experimental evidence demonstrating negative effects of increased foraging and parental effort, the physiological mechanisms underlying costs associated with high workload remain poorly understood. To examine how high workload affects haematology, oxidative stress and reproductive output, we experimentally manipulated foraging effort in captive zebra finches, Taeniopygia guttata, using a previously described technique, and allowed individuals to breed first in low foraging effort conditions and then in high foraging effort conditions. We found that birds upregulated haematocrit and haemoglobin concentration in response to training. Birds subjected to increased workload during reproduction had lower fecundity, although final reproductive output was not significantly different than that of controls. Offspring of parents subjected to high workload during reproduction also had higher oxidative stress when they were 90 days of age. Total antioxidant capacity and reactive oxygen metabolites of birds responded differently in the two breeding attempts, but we did detect an overall increase in oxidative stress in response to training in either attempt, which could explain the lower fecundity observed in birds subjected to increased workload during reproduction.Mantis shrimp commonly inhabit seafloor environments with an abundance of visual features including conspecifics, predators, prey and landmarks used for navigation. Although these animals are capable of discriminating color and polarization, it is unknown what specific attributes of a visual object are important during recognition. Here, we show that mantis shrimp of the species Neogonodactylus oerstedii are able to learn the shape of a trained target. Further, when the shape and color of a target that they had been trained to identify were placed in conflict, N. oerstedii tended to choose the target of the trained shape over the target of the trained color. Thus, we conclude that the shape of the target was more salient than its color during recognition by N. oerstedii, suggesting that the shapes of objects, such as landmarks or other animals, are important for their identification by the species.Many expressions of phenotype, such as physiological performance, integrate multiple underlying traits to function. Linking component traits to adaptive physiology thus gives insight into mechanisms of selection acting on performance. Genome size (C-value) is a trait that influences physiology in multiple taxa by exerting a nucleotypic effect, constraining cell size and cellular physiology such that whole-organism mass-specific metabolism is reduced with increasing C-value. We tested for this mechanism of C-value function acting in lungless salamanders, plus an unexplored potential mechanism of C-value effects constraining water transport across the body surface to influence cutaneous water loss rates. We found no evidence for a nucleotypic effect on metabolic rates, but we demonstrate a relationship between C-value and water loss physiology. Under warmer experimental conditions, C-value was inversely correlated with water loss and positively correlated with resistance to water loss, which demonstrated adaptive plasticity at higher temperatures. We hypothesize this pattern results from differences in cell size constraining diffusion and evaporation of water from the skin under warm conditions when cutaneous perfusion is reduced. Testing this hypothesis may confirm a previously unappreciated adaptive role for C-value variation in this group, and reveals the possibility that genome size influences physiological exchange across transport barriers more broadly.Introduction.A middle-aged woman with idiopathic longitudinally extensive myelitis underwent repeat MR scan of cervical spine at 5-month follow-up, which showed new non-enhancing T2 hyperintensities, initially reported as myelitis recurrence. However, the hyperintensities involved both lateral corticospinal tracts caudal to the initial lesion and both dorsal columns rostral to the initial lesion and were therefore compatible with Wallerian degeneration. This radiological mimic should be considered in the differential of recurrence of myelitis.Esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers worldwide and evolves often to lung metastasis. P53R175H (homologous to Trp53 R172H in mice) is a common hot spot mutation. How metastasis is regulated by p53R175H in ESCC remains to be investigated. To investigate p53R175H-mediated molecular mechanisms, we used a carcinogen-induced approach in Trp53R172H/- mice to model ESCC. In the primary Trp53R172H/- tumor cell lines, we depleted Trp53R172H (shTrp53) and observed a marked reduction in cell invasion in vitro and lung metastasis burden in a tail-vein injection model in comparing isogenic cells (shCtrl). Furthermore, we performed bulk RNA-seq to compare gene expression profiles of metastatic and primary shCtrl and shTrp53 cells. We identified the YAP-BIRC5 axis as a potential mediator of Trp53 R172H -mediated metastasis. We demonstrate that expression of Survivin, an antiapoptotic protein encoded by BIRC5, increases in the presence of Trp53R172H Furthermore, depletion of Survivin specifically decreases Trp53R172H-driven lung metastasis. Mechanistically, Trp53R172H but not wild-type Trp53, binds with YAP in ESCC cells, suggesting their cooperation to induce Survivin expression. Furthermore, Survivin high expression level is associated with increased metastasis in several GI cancers. Taken together, this study unravels new insights into how mutant p53 mediates metastasis.While changes in MeCP2 dosage cause Rett syndrome (RTT) and MECP2 duplication syndrome (MDS), its transcriptional regulation is poorly understood. Here, we identified six putative noncoding regulatory elements of Mecp2, two of which are conserved in humans. Upon deletion in mice and human iPSC-derived neurons, these elements altered RNA and protein levels in opposite directions and resulted in a subset of RTT- and MDS-like behavioral deficits in mice. Our discovery provides insight into transcriptional regulation of Mecp2/MECP2 and highlights genomic sites that could serve as diagnostic and therapeutic targets in RTT or MDS.

Past studies have inconsistently identified factors associated with independent walking post-stroke. We investigated the relationship between pre-stroke factors and factors collected acutely after stroke and number of days to walking 50 m unassisted using data from A Very Early Rehabilitation Trial (AVERT).

The outcome was recovery of 50 m independent walking, tested from 24 hours to 3 months post-stroke. A set of a priori defined factors (participant demographics age, sex, handedness; pre-stroke hypertension, ischaemic heart disease, hypercholesterolaemia, diabetes mellitus, atrial fibrillation; stroke-related stroke severity, stroke type, ischaemic stroke location, stroke hemisphere, thrombolysis) were investigated for association with independent walking using a cause-specific competing risk Cox proportional hazards model. Respective effect sizes are reported as cause-specific adjusted HR (caHR) adjusted for age, stroke severity and AVERT intervention.

A total of 2100 participants (median age 73 yearbgroups, in particular people with haemorrhagic and severe stroke.Since the 2016 Zika outbreak and the understanding of the teratogenic effect of this infection, there has been a newfound interest in arbovirus infections and their effects on pregnancy, resulting in numerous publications in the last 5 years. However, limited literature focuses on arbovirus infection in different stages of pregnancy and their effect on the neonate. There is currently no consensus management of perinatal acquisition of arboviruses, and current evidence is largely anecdotal observational reports. Teratogens can have different effects on the developing fetus depending on the time of infection, so infections during pregnancy should be analyzed by trimester. A better understanding of arbovirus infection in the perinatal period is required to assist obstetric, neonatal, and pediatric clinicians in making decisions about the management of mother and neonate. Our objective was to assess the evidence of adverse neonatal outcomes for several arboviral infections when contracted during the perinatal period to guide clinicians in managing these patients. There are 8 arboviruses for which neonatal outcomes from maternal acquisition in the perinatal period have been reported, with the most data for dengue and Chikungunya virus infections. The evidence reviewed in this article supports the adoption of preventive strategies to avoid ticks and mosquitoes close to the date of delivery. For the other arbovirus infections, further community-based cohort studies during outbreaks are required to evaluate whether these infections have a similar teratogenic impact.

Most infants hospitalized with respiratory syncytial virus (RSV) do not meet common "high-risk" criteria and are otherwise healthy. The objective of this study was to quantify the risks and relative importance of socioeconomic factors for severe, early-life RSV-related illness. We hypothesized several of these factors, particularly those indicating severe social vulnerability, would have statistically significant associations with increased RSV hospitalization rates and may offer impactful targets for population-based RSV prevention strategies, such as prophylaxis programs.

We used linked health, laboratory, and sociodemographic administrative data for all children born in Ontario (2012-2018) to identify all RSV-related hospitalizations occurring before the third birthday or end of follow-up (March 31, 2019). We estimated rate ratios and population attributable fractions using a fully adjusted model.

A total of 11 782 RSV-related hospitalizations were identified among 789 484 children. Multiple socioeconomic factors were independently associated with increased RSV-related admissions, including young maternal age, maternal criminal involvement, and maternal history of serious mental health and/or addiction concerns.